It is a bit of a mystery as to why a body cell develops into an eye or and liver of whatever. For the first time, scientists have altered natural bioelectrical communication among cells to directly specify the type of new organ to be created at a particular location within a vertebrate organism. Using genetic manipulation of membrane voltage in Xenopus (frog) embryos, biologists at Tufts University's School of Arts and Sciences were able to cause tadpoles to grow eyes outside of the head area.

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The researchers achieved most unexpected results when they manipulated the membrane voltage of cells in the tadpole's back and tail, well outside of where the eyes could normally form. "The hypothesis is that for every structure in the body there is a specific membrane voltage range that drives organogenesis," said Tufts post-doctoral fellow Vaibhav P. Pai Ph.D., first author of the paper, entitled "Transmembrane Voltage Potential Controls Embryonic Eye Patterning in Xenopus laevis."

In animal development, organogenesis is the process by which the ectoderm, endoderm, and mesoderm develop into the internal organs of the organism.

Pai noted, "These were cells in regions that were never thought to be able to form eyes. This suggests that cells from anywhere in the body can be driven to form an eye."

What this implies is that by varying a simple electric current or charge new organs may be triggered to grow anywhere in a body. It is a long way to go for true regeneration but it is promising.

To do this, they changed the voltage gradient of cells in the tadpoles' back and tail to match that of normal eye cells. The eye-specific gradient that drove the cells in the back and tail—which would normally develop into other organs—to develop into eyes.

These findings break new ground in the field of biomedicine because they identify an entirely new control mechanism that can be capitalized upon to induce the formation of complex organs for transplantation or regenerative medicine applications, according to Michael Levin, Ph.D., professor of biology and director of the Center for Regenerative and Developmental Biology at Tufts University's School of Arts and Sciences. Levin is senior and corresponding author on the work published in the journal Development. online December 7 2011, in advance of print.

"These results reveal a new regulator of eye formation during development, and suggest novel approaches for the detection and repair of birth defects affecting the visual system," he said. "Aside from the regenerative medicine applications of this new technique for eyes, this is a first step to cracking the bioelectric code."

They found that these cells expressed genes that are involved in building the eye called Eye Field Transcription Factors (EFTFs). Sectioning of the embryo through the developed eye and analyzing the eye regions under fluorescence microscopy showed that the hyperpolarized cells contributed to development of the lens and retina. The researchers hypothesized that these cells turned on genes that are necessary for building the eye.

The researchers were able to show that by changing the bioelectric code, or depolarizing these cells, affected normal eye formation. They injected the cells with mRNA encoding ion channels, which are a class of gating proteins embedded in the membranes of the cell. Like gates, each ion channel protein selectively allows a charged particle to pass in and out of the cell.

Further, the Tufts biologists were also able to show that they could control the incidence of abnormal eyes by manipulating the voltage gradient in the embryo. "Abnormalities were proportional to the extent of disruptive depolarization," said Pai. "We developed techniques to raise or lower voltage potential to control gene expression."